The hearts of bivalve molluscs are structural and functional analogs of the vertebrate myocardium, and are therefore favorable model systems for studying the general mechanisms underlying rhythmical activity in cardiac muscle. This investigation concerns two agents which modify rhythmicity: 5-hydroxytryptamine (5HG) and FMRFamide. 5HT is the molluscan cardioexcitatory neurotransmitter; its action closely parallels that of adrenaline on the vertebrate heart. FMRFamide (Phe-Met-Arg-Phe-NH2) a molluscan neuropeptide, is a cardioexcitatory and anti-arrhythmic agent, incuding spontaneous rhythmical activity in quiescent molluscan hearts and augmenting the beat of active ones. Hearts and other muscles from various molluscan species are being used to establish the relationship between the mechanical actions of FMRFamide and 5HT and their effect on intracellular levels of cyclic AMP and cyclic GMP. Electrical responses to 5HT and FMRFamide are being recorded by the sucrose gap technique; ionic dependence and structure-activity relations will be described. The possibility that FMRFamide is a neurosecretory product will be tested by subcellular fractionation of bivalve ganglia, electron microscopy and release studies. The taxonomic distribution of FMRFamide and analogous peptides is being investigated. A radioimmunoassay (RIA) for FMRFamide is being developed to complement the very sensitive microbioassay now in use.